This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Objective: To explore the possibility that dietary restriction retards aging processes in a nonhuman primate species, this Program Project has provided a wealth of new information about the biology of aging and how the manipulation of diet can influence the process of growing old. Rhesus monkeys eating 30 percent fewer calories of a nutritionally complete diet exhibit better health than study controls. Reduced caloric intake seems to slow basic aging processes and may extend the maximum life span in primates, as has been shown in rodents. Diabetes develops less frequently in monkeys on a restricted diet. Animals allowed to eat freely have a greater incidence of diabetic or pre-diabetic conditions. Fasting basal insulin and glucose concentrations are lower in monkeys on a restricted diet. Both fat mass and fat-free mass were lower in monkeys on a restricted diet. Monkeys on a reduced-calorie diet have fewer signs of spinal arthritis, a condition that manifests itself with age in both rhesus monkeys and humans. Fewer calories may reduce the risk of vascular disease. Caloric restriction altered circulating LDL in a manner that may inhibit atherogenesis. Caloric restriction retards several age-dependent physiological and biochemical changes in skeletal muscle, including oxidative damage. Controlled caloric restriction has not disrupted menstrual cycles of female monkeys. The next period of study should be even more insightful as the oldest monkeys in the study are now truly old. During this phase, age-related diseases and disorders appear more frequently, including adult-onset diabetes, osteoporosis, cancers, obesity, hypertension and the loss of skeletal muscle mass. This research used Animal Services and Research Services. PUBLICATIONS: Anderson RM, Shanmuganayagan D, Weindruch R: Caloric restriction and aging: studies in mice and monkeys. Toxicol. Pathol. 37:47-51, 2009. Colman RJ, Anderson RM, Johnson SC, Kastman EK, Kosmatka KJ, Beasley TM, Allison DB, Cruzen C, Simmons HA, Kemnitz JW, Weindruch R: Caloric restriction delays disease onset and mortality in rhesus monkeys. Science 325:201-4, 2009. Cruzen C, Colman RJ. Effects of caloric restriction on cardiovascular aging in non-human primates and humans. Clin. Geriatr. Med. 25(4):733-743, 2009. McKiernan SH, Colman R, Lopez M, Beasley TM, Weindruch R, Aiken JM: Longitudinal analysis of early stage sarcopenia in aging rhesus monkeys. Exp. Gerontol. 44:170-6, 2009. McLaren DG, Kosmatka KJ, Oakes TR, Kroenke CD, Kohama SG, Matochik JA, Ingram DK, Johnson SC: A population-average MRI-based atlas collection of the rhesus macaque. Neuroimage 45:52-9, 2009. Park SK, Kim K, Page GP, Allison DB, Weindruch R, Prolla TA: Gene expression profiling of aging in multiple mouse strains: identification of aging biomarkers and impact of dietary antioxidants. Aging Cell 8:484-95, 2009. Rezzi S, Martin FP, Shanmuganayagam D, Colman RJ, Nicholson JK, Weindruch R: Metabolic shifts due to long-term caloric restriction revealed in nonhuman primates. Exp. Gerontol. 44:356-62, 2009.